Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSYK97W)

• DOT Name: Glucose-6-phosphate exchanger SLC37A1 (SLC37A1)
• Synonyms: Glycerol-3-phosphate permease; G-3-P permease; Solute carrier family 37 member 1
• Gene Name: SLC37A1
• UniProt ID: G6PT2_HUMAN
• Pfam ID: PF07690
• Sequence:
  MARLPAGIRFIISFSRDQWYRAFIFILTFLLYASFHLSRKPISIVKGELHKYCTAWDEAD
  VRFSSQNRKSGSAAPHQLPDNETDCGWAPFDKNNYQQLLGALDYSFLCAYAVGMYLSGII
  GERLPIRYYLTFGMLASGAFTALFGLGYFYNIHSFGFYVVTQVINGLVQTTGWPSVVTCL
  GNWFGKGRRGLIMGVWNSHTSVGNILGSLIAGYWVSTCWGLSFVVPGAIVAAMGIVCFLF
  LIEHPNDVRCSSTLVTHSKGYENGTNRLRLQKQILKSEKNKPLDPEMQCLLLSDGKGSIH
  PNHVVILPGDGGSGTAAISFTGALKIPGVIEFSLCLLFAKLVSYTFLFWLPLYITNVDHL
  DAKKAGELSTLFDVGGIFGGILAGVISDRLEKRASTCGLMLLLAAPTLYIFSTVSKMGLE
  ATIAMLLLSGALVSGPYTLITTAVSADLGTHKSLKGNAHALSTVTAIIDGTGSVGAALGP
  LLAGLLSPSGWSNVFYMLMFADACALLFLIRLIHKELSCPGSATGDQVPFKEQ
• Function: Inorganic phosphate and glucose-6-phosphate antiporter. May transport cytoplasmic glucose-6-phosphate into the lumen of the endoplasmic reticulum and translocate inorganic phosphate into the opposite direction. Independent of a lumenal glucose-6-phosphatase. May not play a role in homeostatic regulation of blood glucose levels.
• Tissue Specificity: Expressed in numerous tissues, with highest expression in pancreas, kidney, bone marrow, spleen, liver, small intestine, as well as in fetal brain, liver and spleen.
• Reactome Pathway: Gluconeogenesis (R-HSA-70263)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
3-iodothyronamine	DM3L0F8	Investigative	Glucose-6-phosphate exchanger SLC37A1 (SLC37A1) affects the uptake of 3-iodothyronamine.	[9]

7 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Glucose-6-phosphate exchanger SLC37A1 (SLC37A1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Glucose-6-phosphate exchanger SLC37A1 (SLC37A1).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Glucose-6-phosphate exchanger SLC37A1 (SLC37A1).	[3]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Glucose-6-phosphate exchanger SLC37A1 (SLC37A1).	[4]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Glucose-6-phosphate exchanger SLC37A1 (SLC37A1).	[5]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Glucose-6-phosphate exchanger SLC37A1 (SLC37A1).	[7]
Nitrobenzanthrone	DMN6L70	Investigative	Nitrobenzanthrone decreases the expression of Glucose-6-phosphate exchanger SLC37A1 (SLC37A1).	[8]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Glucose-6-phosphate exchanger SLC37A1 (SLC37A1).	[6]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [5] Differential gene expression in human hepatocyte cell lines exposed to the antiretroviral agent zidovudine. Arch Toxicol. 2014 Mar;88(3):609-23. doi: 10.1007/s00204-013-1169-3. Epub 2013 Nov 30.
• [6] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [7] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [8] 3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway. Cell Biol Toxicol. 2022 Oct;38(5):865-887. doi: 10.1007/s10565-021-09612-1. Epub 2021 May 25.
• [9] Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology. 2009 Apr;150(4):1991-9.